The use and manufacture of enteric dosage forms are well known in the art. Such dosage forms are described in Remington's Pharmaceutical Sciences, 18th Ed., Mack Publishing Co., Easton, Pa. (1990). Enteric dosage forms are useful for protecting the contents of the dosage form from the gastric conditions of the stomach and/or to protect gastric tissue from an irritant material contained in the dosage form. Enteric dosage forms can also be useful in preventing gastric reflux due to the presence of odor-causing liquids, such as fish oil or garlic oil, in the dosage form.
Enteric-coated dosage forms are typically produced by a film coating process, where a thin film layer of an acid-insoluble (enteric) polymer is applied to the surface of a pre-manufactured dosage form, such as a tablet, and to a lesser extent hard and soft capsules. The enteric coating method involves spraying an aqueous or organic solution or suspension of one or more enteric polymers onto tumbling or moving tablets or capsules, followed by drying at elevated temperatures. Enteric dosage forms made by this coating method can suffer from various process-related problems that affect the performance and/or appearance of the coating. For example, “orange peel” surface formation, also known as surface roughness or mottling, may result. More seriously, coat integrity failure may occur, such as cracking or flaking off of the enteric polymer coating. All coating processes present inherent problems, including possible uneven distribution of the coating ingredients, which can occur under multivariate coating processes.
These problems are common to all enteric dosage forms. However, the problems faced during the coating of gelatin or polysaccharide capsules are even more critical due to the delicate and heat sensitive nature of the soft elastic capsule shell. Both hard and soft capsules can undergo thermally induced agglomeration and distortion of the capsule shell. Moreover, the smoothness and elasticity of the capsule surface makes it difficult to form an intact adhering enteric coating, without a subcoating step to improve the surface of the capsule for coating. Finally, the enteric coatings cause the loss of the normally shiny and clear appearance of gelatin capsule shells, which is a major reason for the popularity and acceptance of gelatin capsules.
Attempts to overcome the limitations associated with coated dosage forms have been made. For example, WO 2004/03068 by Banner Pharmacaps, Inc. (“the '068 application”) describes a gel mass that is useful in manufacturing enteric soft or hard shell capsules or enteric tablets without the need for a coating. The gel mass comprises a film-forming, water-soluble polymer, an acid-insoluble polymer and optionally, one or more excipients such as plasticizers, colorants and flavorants. The '068 application, however, discloses the use of synthetic acid-insoluble polymers such as cellulosic polymers and acrylic acid-methacrylic acid copolymers (Eudragit®) which are present in a concentration from 8 to 20% by weight of the wet gel mass.
U.S. Patent Application Publication No. 2003/0175335 by Scott et al, (“the '335 application”) describes film forming compositions containing pectin, at least one film-forming polymer, and a setting system for preparing soft and hard shell capsules. The concentration of pectin is 5 to 60% by weight, preferably 10 to 40% by weight. The concentration of the film-forming polymer is 40 to 95% by weight, preferably 50 to 85% by weight. The '335 application discloses a film containing 5 to 25%, preferably 10 to 20% by weight pectin which is suitable to prepare hard shell capsules with enteric properties.
There exists a need for a gastric resistant film-forming composition that contains a gastric resistant natural polymer at relatively lower concentrations.
Therefore, it is an object of the invention to provide a gastric resistant film-forming composition comprising a gastric resistant film-forming composition which comprises a gastric resistant natural polymer at relatively low concentrations and methods of manufacturing thereof.
It is further an object of the invention to provide a gastric resistant capsule shell, which can encapsulate a liquid, semi-solid, or solid fill, which contains a gastric resistant natural polymer at relatively low concentrations and methods of manufacturing thereof.